This proposal is studying biochemical mechanisms in the clinical condition known as methylmalonic acidemia (MM-emia). Fibroblast-like cell lines cultured from 16 patients with MM-emia, will be studied with respect to the metabolism of propionate and racemic methylmalonyl CoA. The biochemical defect will be further characterized by determining the binding kinetics of vitamin B12 coenzyme with its apoenzyme. Transport of 57Co-hydroxocobalamin in vitro will be measured. In many patients suffering from MM-emia, bouts of ketoacidosis occur. Decreased utilization of circulating ketone bodies via succinyl CoA:3-ketoacid CoA transferase may be responsible for much of the morbidity and mortality in this condition. Cardiac perfusion utilizing acetoacetate and B-hydroxybutyrate in rats will be performed. The ability of vitamin B12 deficient and control animals to metabolize B- hydroxybutyrate and acetoacetate will be compared. Continual monitoring of a four year old male with vitamin B12 responsive methylmalonic acidemia will be performed. Physical, psychomotor and biochemical parameters are being studied.